Adipose Tissue-Derived Mesenchymal Stem Cells Protect Against Amiodarone-Induced Lung Injury in Rats.

Pulmonary fibrosis (PF) is a progressive and irreversible lung disease, characterized by poor prognosis with limited treatment options. Mesenchymal stem cells (MSCs) are multi-potent cells having the ability to self-renew and differentiate into multiple tissues, thus considered a novel treatment option. The present study aimed to investigate the possible antifibrotic effect of undifferentiated adipose tissue-derived mesenchymal stem cell (AD-MSC) therapy on PF experimentally induced in rats using amiodarone (AMD). AMD (30 mg/kg) was given orally, once daily for 12 consecutive weeks to induce lung fibrosis. Following the confirmation of lung damage with histopathological examination, AD-MSCs (2 × 106 and 4 × 106 undifferentiated MSCs) were injected once intravenously, followed by 2 months for treatment. AMD induced focal fibroblastic cells proliferation in the peribronchiolar tissue, as well as in between the collapsed emphysematous alveoli. Also, AMD significantly increased serum and lung homogenate fibroblast growth factor-7 (FGF7), Clara cell protein-16 (CC16), and cytokeratin -19 (CK19) levels, as well as the expression of both iNOS and NFкB in the lung alveoli. Moreover, AMD caused excessive collagen deposition and increased alpha smooth muscle actin (α-SMA) expression. All findings significantly regressed on stem cell therapy in both doses, with superior effect of the high dose, providing evidence that adipose tissue-derived MSCs could be a promising approach for the treatment of PF. Graphical Abstract.

Exposure to Atmospheric Ultrafine Particles Induces Severe Lung Inflammatory Response and Tissue Remodeling in Mice.

Exposure to particulate matter (PM) is leading to various respiratory health outcomes. Compared to coarse and fine particles, less is known about the effects of chronic exposure to ultrafine particles, despite their higher number and reactivity. In the present study, we performed a time-course experiment in mice to better analyze the lung impact of atmospheric ultrafine particles, with regard to the effects induced by fine particles collected on the same site. Trace element and PAH analysis demonstrated the almost similar chemical composition of both particle fractions. Mice were exposed intranasally to FF or UFP according to acute (10, 50 or 100 µg of PM) and repeated (10 µg of PM 3 times a week during 1 or 3 months) exposure protocols. More particle-laden macrophages and even greater chronic inflammation were observed in the UFP-exposed mice lungs. Histological analyses revealed that about 50% of lung tissues were damaged in mice exposed to UFP for three months versus only 35% in FF-exposed mice. These injuries were characterized by alveolar wall thickening, macrophage infiltrations, and cystic lesions. Taken together, these results strongly motivate the update of current regulations regarding ambient PM concentrations to include UFP and limit their emission.